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Response: Ly6G: a work in progress

Peter A. Nigrovic

We are grateful to Drs Yipp and Kubes for their attention to our recent work and for adding an important new piece to the puzzle of Ly6G and its function in neutrophil-mediated immunity.1,2

We find no incompatibility between their observations and our own. As is well recognized, the pathways mediating neutrophil migration differ with site and stimulus. In particular, whereas LFA-1 is strictly required for neutrophil migration at the initiation phase of K/BxN arthritis,3,4 other pathways can often compensate for β2 integrin deficiency in the context of bacterial infection.5,6 Because we found that Ly6G ligation attenuated β2 integrin–dependent migration, but not β2 integrin–independent migration,2 it is not clear that an effect would have been expected in the Staphylococcus aureus cellulitis model used by Drs Yipp and Kubes.

However, we recognize that divergent dependence on β2 integrins cannot be the whole story. The Kubes laboratory has employed conjugated anti–Gr-1 as an in vivo tool in several important studies using models of sterile inflammation in which β2 integrins play a demonstrable role.6,7 Further investigation will be required to determine the relevant differences between these experimental systems and those used in our work.

We therefore interpret the findings of Drs Yipp and Kubes as complementary to, rather than in conflict with, our own. Together, these studies raise new and interesting questions. What are the conditions under which Ly6G-binding ligation alters migration? What is the role of Ly6G in the normal course of neutrophil physiology? What does this role of Ly6G tell us about human neutrophil biology? We look forward to working with the Kubes laboratory and others to answer these important questions.

Authorship

Acknowledgments: This work was supported by grants from the Arthritis National Research Foundation, the Charles H. Hood Foundation, the Harvard Skin Disease Research Center, and the Cogan Family Foundation (to P.A.N).

Contribution: P.A.N. wrote the response, which was circulated among all coauthors of the original article to incorporate their input and secure their approval.

Conflict-of-interest disclosure: The author declares no competing financial interests.

Correspondence: Peter A. Nigrovic, MD, Brigham and Women's Hospital, Division of Rheumatology, Immunology and Allergy, Smith Bldg, Rm 516c, One Jimmy Fund Way, Boston, MA 02115; e-mail: pnigrovic{at}partners.org.

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